Down Syndrome, the most common genetic cause of mental retardation in the United States, is caused by trisomy of the smallest human chromosome, chromosome 21. Individuals with Down Syndrome are at increased risk for congenital heart disease, leukemia and Alzheimer Disease. Recently a gene responsible for Familial Alzheimer Disease, a gene for the beta amyloid protein isolated from the brain lesions of patients with Alzheimer Disease, and at least one oncogene, the ets-2 oncogene, have been mapped to chromosome 21. In order to understand which genes on chromosome 21 contribute to the pathology observed in trisomy 21, and also to understand how these genes contribute to human development, it is necessary to devise a detailed molecular map of this human chromosome. It is the goal of the research proposed here to construct this map using somatic cell and molecular genetics approaches. In particular somatic hybrids between Chinese hamster ovary cells and human cells containing translocations involving chromosome 21 will be prepared which will isolate the translocation 21 chromosomes away from all other human chromosomes. Standard and pulsed-field gel electrophoresis and Southern blot hybridization analysis with a large number (<75) of unique and repeated DNA sequence probes will be carried out on all the hybrids. In this way the chromosome 21 translocation junction points can used as landmarks on the map of chromosome 21. With this information as a base, analysis of the organization of the DNA of chromosome 21 will be undertaken. In this way information will be generated which should be of critical importance for our understanding of human development and mental retardation. These studies any serve as a model for development of a gene map for any region of the human genome of interest.